Gordon C J, Fogelson L, Richards J, Highfill J
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Toxicol Lett. 1991 Dec;59(1-3):161-8. doi: 10.1016/0378-4274(91)90068-h.
This study examined the relationship between inhibition of cholinesterase activity (CA) and thermoregulatory response in the rat following exposure to the organophosphate (OP), diisopropyl fluorophosphate (DFP). Male Long-Evans rats were injected with DFP dissolved in peanut oil in doses ranging from 0 to 1.5 mg/kg (s.c.). Colonic (Tcol) and tail skin temperature (Ttail) were recorded at 0, 1, 2 and 3 h post-injection. At 3 h post-injection the rat was sacrificed and a blood sample was taken by cardiac puncture and analyzed for CA. There was a biphasic dose effect of DFP on Tcol with slight but significant elevation in Tcol in the dose range of 0.01-0.5 mg/kg and a significant depression in Tcol at doses of 1.0 and 1.5 mg/kg. There was a dose-dependent fall in CA with DFP administration in the erythrocyte, plasma, and whole blood fractions. Hypothermia was associated with 80-87% inhibition in CA, whereas the elevation in Tcol was associated with 20-70% inhibition in CA. DFP also elicited significant elevations in Ttail. Overall, the data fail to demonstrate any clear relationship between inhibition of blood CA and thermoregulatory response following exposure to DFP. However, the elevation in Tcol following relatively low doses of DFP may be of relevance to the frequently reported symptom of fever in humans exposed to OP agents.
本研究检测了大鼠暴露于有机磷酸酯(OP)二异丙基氟磷酸酯(DFP)后,胆碱酯酶活性(CA)抑制与体温调节反应之间的关系。雄性Long-Evans大鼠皮下注射溶解于花生油中的DFP,剂量范围为0至1.5毫克/千克。在注射后0、1、2和3小时记录结肠温度(Tcol)和尾皮温度(Ttail)。注射后3小时处死大鼠,通过心脏穿刺采集血样并分析CA。DFP对Tcol有双相剂量效应,在0.01 - 0.5毫克/千克剂量范围内Tcol略有但显著升高,而在1.0和1.5毫克/千克剂量时Tcol显著降低。随着DFP给药,红细胞、血浆和全血部分的CA呈剂量依赖性下降。体温过低与CA抑制80 - 87%相关,而Tcol升高与CA抑制20 - 70%相关。DFP还引起Ttail显著升高。总体而言,数据未能证明暴露于DFP后血液CA抑制与体温调节反应之间存在任何明确关系。然而,相对低剂量DFP后Tcol的升高可能与接触OP制剂的人类中频繁报道的发热症状相关。